Biomarkers of systemic inflammation are associated with disease severity and metabolic syndrome in patients with hidradenitis suppurativa.

Background: Biomarkers associated with disease severity and comorbid metabolic syndrome (MetS) in patients with hidradenitis suppurativa (HS) are lacking. Objective: To identify biomarkers associated with disease severity and comorbid MetS in patients with HS. Methods: Data on hospital outpatients with HS were obtained through clinical examination and interviews. Indicators of systemic inflammation; C-reactive protein (CRP), erythrocyte sedimentation-rate (ESR), neutrophil/lymphocyte-ratio (NLR), platelet/lymphocyte-ratio (PLR), monocyte/lymphocyte-ratio (MLR), platelet/neutrophil-ratio (PNR), pan-immune-inflammation-value (PIV), and systemic-immune-inflammatory-index (SII), were calculated from blood samples. Results: Seven hundred patients were included; of those 444 (63.4%) and 256 (36.6%) were female and male, respectively, with a median age of 38.3 years (IQR = 27.9-51.0). Increasing CRP, ESR, NLR, PIV, and SII (P < .001) were significantly associated with increasing Hurley-stage and international hidradenitis suppurativa severity score system 4 (IHS4)-score in adjusted analysis. A doubling in CRP (OR 1.59 (1.36-1.85), P < .001), ESR (OR 1.39 (1.17-1.66), P < .001) and PIV (OR 1.41 (1.12-1.77) P = .002) was associated with MetS in adjusted analysis. ESR was the best estimator for severe IHS4-score (AUC = 0.72 (0.66-0.77), P < .001) and Hurley III (AUC = 0.79 (0.73-0.85), P < .001) whereas CRP was best for MetS (AUC = 0.67 (0.62-0.72), P < .001). Limitations: Patients in a hospital setting tend to have more severe disease. Conclusion: Biomarkers like CRP, ESR, and PIV measuring systemic inflammation were associated with disease severity and comorbid MetS in patients with HS.

Sustained Improvements in Clinical and Patient-Reported Outcomes and Quality of Life Through 5 Years Among Ixekizumab-Treated Patients with Complete Clearance of Scalp Psoriasis by Week 60.

INTRODUCTION: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of moderate-to-severe plaque psoriasis. Since scalp psoriasis can be burdensome and challenging to treat with non-systemic therapies, this post hoc analysis focused on scalp psoriasis in patients with moderate-to-severe plaque psoriasis and baseline scalp involvement. The analysis considered a holistic concept of clearance through 5 years of ixekizumab treatment. METHODS: Ixekizumab-treated patients with baseline scalp involvement were pooled from three multicenter, randomized, double-blind, placebo-controlled, phase 3 trials (integrated UNCOVER-1/2 and UNCOVER-3). Analyses were performed on a subpopulation of patients who achieved complete resolution of scalp psoriasis at Week 60 (i.e., Week 60 Psoriasis Scalp Severity Index [PSSI-0] responders) and on the overall patient population (i.e., Week 60 PSSI-0 responders and non-responders), which was used as a reference. Clinical outcomes (PSSI), patient-reported outcomes (Itch Numeric Rating Scale [NRS] score, Skin Pain Visual Analogue Scale [VAS]), quality of life (Dermatology Life Quality Index [DLQI]), and concurrent outcomes were assessed from baseline through 5 years. Descriptive statistics of observed data were reported. RESULTS: After 60 weeks of ixekizumab treatment, 88.4% (UNCOVER-1/2) and 75.9% (UNCOVER-3) of patients with baseline scalp involvement achieved complete clearance (PSSI-0) of scalp psoriasis. Substantial improvements in the clinical outcomes (PSSI), patient-reported outcomes (Itch NRS, Skin Pain VAS), and quality of life (DLQI) were achieved by Week 60 and sustained through Week 264 in the Week 60 PSSI-0 responders and in the overall patient population. Additionally, a significant proportion of Week 60 PSSI-0 responders achieved concurrent complete scalp and skin clearance and quality of life improvement through 5 years. CONCLUSIONS: Continued treatment with ixekizumab provided long-term sustained scalp clearance over 5 years to patients with moderate-to-severe plaque psoriasis and baseline scalp involvement, and holistic improvements occurred across clinical outcomes, patient-reported outcomes, and quality of life. CLINICAL TRIAL NUMBERS: NCT01474512 (UNCOVER-1), NCT01597245 (UNCOVER-2), and NCT01646177 (UNCOVER-3).

Erenumab for Treatment of Persistent Erythema and Flushing in Rosacea: A Nonrandomized Controlled Trial.

Importance: Treatment of erythema and flushing in rosacea is challenging. Calcitonin gene-related peptide (CGRP) has been associated with the pathogenesis of rosacea, raising the possibility that inhibition of the CGRP pathway might improve certain features of the disease. Objective: To examine the effectiveness, tolerability, and safety of erenumab, an anti-CGRP-receptor monoclonal antibody, for the treatment of rosacea-associated erythema and flushing. Design, Setting, and Participants: This single-center, open-label, single-group, nonrandomized controlled trial was conducted between June 9, 2020, and May 11, 2021. Eligible participants included adults with rosacea with at least 15 days of either moderate to severe erythema and/or moderate to extreme flushing. No concomitant rosacea treatment was allowed throughout the study period. Visits took place at the Danish Headache Center, Copenhagen University Hospital, Rigshospitalet in Copenhagen, Denmark. Participants received 140 mg of erenumab subcutaneously every 4 weeks for 12 weeks. A safety follow-up visit was performed at week 20. Data analysis occurred from January 2023 to January 2024. Intervention: 140 mg of erenumab every 4 weeks for 12 weeks. Main Outcomes and Measures: The primary outcome was mean change in the number of days with moderate to extreme flushing during weeks 9 through 12, compared with the 4-week run-in period (baseline). The mean change in number of days with moderate to severe erythema was a secondary outcome. Adverse events were recorded for participants who received at least 1 dose of erenumab. Differences in means were calculated with a paired t test. Results: A total of 30 participants (mean [SD] age, 38.8 [13.1] years; 23 female [77%]; 7 male [23%]) were included, of whom 27 completed the 12-week study. The mean (SD) number of days with moderate to extreme flushing was reduced by -6.9 days (95% CI, -10.4 to -3.4 days; P < .001) from 23.6 (5.8) days at baseline. The mean (SD) number of days with moderate to severe erythema was reduced by -8.1 days (95% CI, -12.5 to -3.7 days; P < .001) from 15.2 (9.1) days at baseline. Adverse events included transient mild to moderate constipation (10 participants [33%]), transient worsening of flushing (4 participants [13%]), bloating (3 participants [10%]), and upper respiratory tract infections (3 participants [10%]), consistent with previous data. One participant discontinued the study due to a serious adverse event (hospital admission due to gallstones deemed unrelated to the study), and 2 participants withdrew consent due to lack of time. Conclusions and Relevance: These findings suggest that erenumab might be effective in reducing rosacea-associated flushing and chronic erythema (participants generally tolerated the treatment well, which was consistent with previous data), and that CGRP-receptor inhibition holds potential in the treatment of erythema and flushing associated with rosacea. Larger randomized clinical trials are needed to confirm this finding. Trial Registration: ClinicalTrials.gov Identifier: NCT04419259.

Elevated plasma levels of calcitonin gene-related peptide in individuals with rosacea: A cross-sectional case-control study.

BACKGROUND: Understanding the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of rosacea might provide new therapeutic avenues for individuals with this disease. OBJECTIVE: To compare plasma levels of CGRP between individuals with rosacea and healthy controls. METHODS: In this cross-sectional case-control study conducted in Copenhagen, Denmark, we collected blood samples from the antecubital vein from adults with rosacea and from healthy controls. RESULTS: We enrolled 123 individuals with rosacea and 68 healthy controls. After adjusting for age and sex, plasma levels of CGRP were significantly higher in individuals with rosacea (mean, 95% confidence interval: 140.21 pmol/L, 128.50-151.92 pmol/L), compared with controls (110.77 pmol/L, 99.91-120.14 pmol/L, p = 0.002). Plasma levels of CGRP were not affected by age, sex, BMI, concomitant migraine, rosacea sub- or phenotype, concomitant disease or current treatment. LIMITATIONS: Participants were not age-, sex- and BMI-matched. CONCLUSIONS AND RELEVANCE: Elevated plasma levels of CGRP in individuals with rosacea suggest a role of CGRP in the pathogenesis of rosacea. Targeting CGRP signalling might hold therapeutic promise in people affected by this disease. GOV LISTING: NCT03872050.

Characteristics and Management of Patients with Alopecia Areata and Selected Comorbid Conditions: Results from a Survey in Five European Countries.

INTRODUCTION: Alopecia areata (AA) is an autoimmune condition that causes non-scarring hair loss and can impose a high psychosocial burden on patients. The presence of comorbid conditions may impact the management of AA in clinical practice. This analysis aims to describe disease characteristics and management of AA in patients with concomitant atopic, autoimmune, and psychiatric comorbid conditions. METHODS: Data were collected from the Adelphi Disease Specific Programme™, a cross-sectional survey of physicians and their adult patients with AA conducted in France, Germany, Italy, Spain, and the UK between October 2021 and June 2022. Patients' disease severity was based on physician's definition. Physician-reported data on demographics, AA clinical characteristics, comorbid conditions, and information related to AA therapies were analyzed. Analyses were descriptive. RESULTS: Overall, 239 dermatologists provided data for 2083 patients, of which 558 patients (27%) had at least one atopic, autoimmune, or psychiatric comorbid conditions. The most common comorbid conditions were atopic dermatitis, autoimmune thyroid disease, and anxiety. The mean (standard deviation) patient age for the three comorbidity groups was 37.6 years (12.1) and 56% of the patients were women (n = 313). In the three comorbidity groups, 51%, 50%, and 55% of patients with atopic, autoimmune, and psychiatric comorbidities had severe AA with disease progression reported as worsening in 30%, 28%, and 30%, respectively, whereas in the group with no comorbidities, 37% were described as having severe AA and 21% getting worse. Scalp hair loss was the primary sign reported across the three groups of comorbid conditions (atopic, 91%; autoimmune, 91%; psychiatric, 88%). Patients with preselected comorbidities presented more frequently AA-related signs and symptoms beyond scalp hair loss than patients without comorbid conditions. These patients were also more likely to receive topical calcineurin inhibitors, topical immunotherapy, conventional systemic immunosuppressants, and oral Janus kinase inhibitors for the treatment of their AA. CONCLUSION: This analysis provided insights into the burden and management of AA in patients presenting with atopic, autoimmune, and psychiatric comorbid conditions in five European countries.

Effects of oral roflumilast therapy on body weight and cardiometabolic parameters in patients with psoriasis - results from a randomized controlled trial (PSORRO).

BACKGROUND: Weight loss is reported with oral roflumilast, which is approved for chronic obstructive pulmonary disease (COPD). Recently, the drug has shown efficacy in psoriasis, a disease strongly linked to overweight/obesity. OBJECTIVE: To describe the effects of oral roflumilast on body weight and cardio-metabolic parameters in patients with psoriasis. METHODS: Posthoc analyses from the PSORRO study, where patients with moderate-to-severe plaque psoriasis were randomized 1:1 to oral roflumilast 500 µg once-daily or placebo for 12 weeks, followed by active, open-label treatment through week 24 in both groups. Changes in body weight, blood pressure, gastrointestinal symptoms, and laboratory tests were registered. No lifestyle or dietary interventions were applied. RESULTS: Forty-six patients were randomized. Baseline characteristics across groups were comparable; mean weight was 103.6 kg. In patients receiving roflumilast, median weight change was -2.6% and -4% at week 12 and 24, respectively. Corresponding numbers were 0.0% and 1.3% in patients initially allocated to placebo. Reduced appetite was more frequent with active therapy. No changes in blood pressure or laboratory tests were observed. LIMITATIONS: Posthoc analyses and low numbers. CONCLUSION: Oral roflumilast induced weight loss and reduced appetite, which support the growing evidence of roflumilast as an attractive treatment alternative for patients with psoriasis.

Correlation between Dermatology Life Quality Index and Psoriasis Area and Severity Index in Patients with Psoriasis: A Cross-sectional Global Healthcare Study on Psoriasis.

Quality of life impairment in dermatology patients and severity of psoriasis are quantified by the Dermatology Life Quality Index (DLQI) and the Psoriasis Area and Severity Index (PASI), respectively. The aim of this study is to compare the correlation between PASI and DLQI in patients from different geographical areas and to identify predictors of high DLQI across geographical regions. Correlations between PASI and DLQI were evaluated using Spearman's rank correlation tests and quantile regression. The study included 1,158 patients with psoriasis, with a median (interquartile range) PASI and DLQI of 6.0 (3.0-12.0) and 8.0 (4.0-15.0), respectively. Correlations were demonstrated between PASI and DLQI, both overall and stratified by geographical region. Quantile (median) regression yielded coefficients of 0.75 (95% confidence interval (95% CI) 0.62, 0.88) for Switzerland, 0.50 (95% CI 0.42, 0.58) for Latin America, 0.34 (95% CI 0.16, 0.51) for Asia, and 0.31 (95% CI 0.08, 0.53) for the USA. Current age, age at diagnosis, sex, body mass index, and psoriasis arthritis affected DLQI in Latin America, while education had an impact among patients treated in Switzerland. Few countries were included within each continent; hence, more data from different countries are necessary for generalizability. The study showed correlations between PASI and DLQI among patients in all included geographical regions. The patients' characteristics affecting DLQI vary worldwide.

Response Types and Factors Associated with Response Types to Biologic Therapies in Patients with Moderate-to-Severe Plaque Psoriasis from Two Randomized Clinical Trials.

INTRODUCTION: This study aimed to understand treatment response dynamics, including factors associated with favorable response, among patients with moderate-to-severe psoriasis who received guselkumab, adalimumab, or secukinumab. METHODS: These post hoc analyses used data from the phase III clinical trials ECLIPSE and VOYAGE 1, which were conducted between September 2021 and November 2022. On the basis of absolute Psoriasis Area and Severity Index (aPASI) scores, patients were divided into short-term response types (SRT1-6, based on week 20-48 response) and long-term response types (LRT1-4, based on week 52-252 response). Response types (RTs) were based on aPASI cutoffs deemed clinically relevant by the investigators; SRT1/LRT1 were the most favorable response types. Baseline characteristics were compared across RTs, and logistic regression analyses established factors associated with SRT1/LRT1. RESULTS: Overall, 1045, 662, and 272 patients were included in the ECLIPSE short-term, VOYAGE 1 short-term, and VOYAGE 1 long-term analyses, respectively. Mean age, body mass index (BMI), baseline aPASI score, and body surface area were lower in SRT1 than SRT6. In VOYAGE 1, adalimumab treatment, high BMI, and current/former smoking status resulted in less favorable responses. In the VOYAGE 1 long-term analysis, patients in LRT4 had the highest baseline aPASI score, were older, and were more often obese compared with other LRT groups. Regression analyses showed that SRT1 (both treatments) in VOYAGE 1 and ECLIPSE, and LRT1 (guselkumab group) in the VOYAGE 1 long-term analysis, were associated with week 16 aPASI response. In VOYAGE 1, SRT1 was associated with psoriasis duration and smoking status. CONCLUSIONS: Early treatment response and baseline characteristics, including smoking, psoriasis duration, and obesity, may be associated with longer-term response to biologics. TRIAL REGISTRATION NUMBERS: ECLIPSE: NCT03090100, VOYAGE 1: NCT02207231.

Characteristics and drivers of fatigue in patients with psoriasis and psoriatic arthritis: A cross sectional study.

BACKGROUND: A multitude of factors may influence fatigue in psoriasis and psoriatic arthritis (PsA); however, their individual fatigue components have not been thoroughly examined. OBJECTIVES: To explore characteristics of fatigue and its potential drivers in a cohort of patients with psoriasis with or without PsA. METHODS: Adults with psoriasis and a nonpsoriasis control group completed the Multidimensional Fatigue Inventory-20 questionnaire. Patients with psoriasis also reported joint pain intensity, pruritus, skin pain, and sleep problems using a numerical rating scale. Linear regression models were applied to continuous outcomes, and beta coefficients (ß) for the slopes were estimated with 95% confidence intervals (CIs). RESULTS: Among 2741 adults with psoriasis (of which 593 also had PsA) and 3788 controls, the impact on total fatigue was greatest for PsA (ß = 5.22; 95% CI, 3.55-6.90), followed by psoriasis (ß = 2.10; 95% CI, 0.96-3.25), compared with the general population (Ptrend < .0001). Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (ß = 2.23 [95% CI, 2.03-2.44] for each 1-point increase in joint pain numerical rating scale score). LIMITATIONS: We lacked information on the effect of pharmacotherapy. CONCLUSIONS: These findings highlight the importance of a symptom-based approach when treating psoriasis, rather than focusing on objective severity measures alone.

Defining disease severity in atopic dermatitis and psoriasis for the application to biomarker research- an inter-disciplinary perspective.

More severe atopic dermatitis (AD) and psoriasis are associated with a higher cumulative impact on quality of life, multimorbidity and healthcare costs. Proactive, early intervention in those most at risk of severe disease may reduce this cumulative burden and modify the disease trajectory to limit progression. The lack of reliable biomarkers for this at-risk group represents a barrier to such a paradigm shift in practice. To expedite discovery and validation, the BIOMAP consortium (Biomarkers in AD and Psoriasis, a large-scale European, inter-disciplinary research initiative) has curated clinical and molecular data across diverse study designs and sources including cross-sectional and cohort studies (small scale through to large multi-centre registries), clinical trials, electronic health records and large-scale population-based biobanks. We map all dataset disease severity instruments and measures to three key domains (symptoms, inflammatory activity and disease course), and describe important co-dependencies and relationships across variables and domains. We prioritise definitions for more severe disease with reference to international consensus, reference standards and/or expert opinion. Key factors to consider when analysing datasets across these diverse study types include explicit early consideration of biomarker purpose and clinical context, candidate biomarkers associated with disease severity at a point in time and over time and how they are related, taking the stage of biomarker development into account when selecting disease severity measures for analyses and, validating biomarker associations with disease severity outcomes using both physician- and patient-reported measures and across domains. The outputs from this exercise will ensure coherence and focus across the BIOMAP consortium so that mechanistic insights and biomarkers are clinically relevant, patient-centric and more generalisable to current and future research efforts.

The agreement between consumer-driven self-assessment of psoriasis severity and physician-assessed severity based on patient-taken photographs is weak: cross-sectional study.

INTRODUCTION: Digital advancements have given access to huge amounts of real-world data (RWD) widely used for dermatological research. OBJECTIVES: To investigate the agreement between consumer-driven self-assessed psoriasis severity and physician-assessed severity based on photographs. METHODS: Customer IDs in the Nøie database (Danish skincare company) from 2009 to 2022 with a smartphone photograph of psoriasis vulgaris on the body and a corresponding completed questionnaire were included. Smartphone photographs were evaluated by a physician assessing erythema, induration, and scaling on a scale from 0-4 based on Psoriasis Area Severity Index (PASI). Self-assessment was done on a scale from 0 to 10 and converted to 0-4 scale (0 converted to 0; 1-3 to 1; 4-6 to 2; 7-8 to 3; and 9-10 to 4). Intraclass correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated. RESULTS: In total 187 patients (63% women) with mean age 38 years were included. Self-assessment scores were higher than physician-assessment scores for all groups, and scaling was closest to the physician-assessment whilst erythema and induration had a greater distance between the physicians' and patients' assessment. The correlation between self-assessed and physician-assessed psoriasis severity for all patients was 0.23 (95% CI 0.0-0.92); 0.34 (95% CI 0.0-0.95) for chronic patients, and 0.09 (-0.01-0.82) for non-chronic patients. The agreement was better for men 0.53 (-0.02-0.98) than for women 0.12 (-0.01-0.84). CONCLUSION: There was weak agreement between self-assessed psoriasis severity and photographically assessed severity by the physician. Consumer-driven RWD should be interpreted with caution.

Adverse events from topical corticosteroid use in chronic hand eczema - Findings from the Danish Skin Cohort.

Background: Topical corticosteroids (TCS) are used to treat most patients with chronic hand eczema (CHE), but knowledge about TCS-related adverse events in CHE is limited. Objectives: To investigate patient-reported adverse events to TCS in CHE patients. Methods: Data on adverse events related to TCS use in patients with CHE were analyzed from the Danish Skin Cohort; a prospective survey of a hospital cohort. We assessed patients' knowledge about TCS use and adverse event risks, and preference of TCS versus a nonsteroidal topical alternative. Results: Of 724 adults with CHE (64.0% women; mean age 57.5 [standard deviation 12.8] years), 64.1% reported skin atrophy, 41.4% cracks/fissures, 23.9% bleeding, 45.9% pain/stinging sensation, 40.0% reduced hand dexterity, and 40.2% worsening of CHE signs or symptoms from using TCS. We observed CHE-severity-dependent associations (all groups; P < .0001). Most patients (76.4%) would prefer a nonsteroidal option, 10.9% were neutral/indifferent, and 12.7% would prefer TCS for CHE. The median numerical rating scale-score (ranging from 0 to 10) was 10 (interquartile range 6-10) for preferring a nonsteroidal topical treatment. Limitations: Differences across TCS formulations were unexplored. Conclusion: TCS-related cutaneous adverse events were common. There is a desire from patients for novel steroid-free topical alternatives for CHE treatment.

Risk Factors that Impact Treatment with Oral Janus Kinase Inhibitors Among Adult Patients with Atopic Dermatitis: A Nationwide Registry Study.

The European Medicines Agency recently limited the use of oral Janus kinase inhibitors in certain patient populations, including those with atopic dermatitis. This cross-sectional study used the Danish national registers and Danish Skin Cohort to assess the prevalence of risk factors that potentially impact choice of treatment with oral Janus kinase inhibitors in adult patients with atopic dermatitis. From the Danish national registers and Danish Skin Cohort, 18,618 and 3,573 adults with atopic dermatitis, respectively, were identified. Half of the patients (49.5%) had, at some point, been registered to have at least 1 risk factor that could impact treatment with oral Janus kinase inhibitors. Non-modifiable risk factors recorded were cancer (5.6%), major adverse cardiovascular events (2.6%), venous thromboembolism (2.0%), smoking history (15.6%), and age ≥ 65 years (12.4%). Among patients ≥ 65 years of age, the mean (standard deviation) number of risk factors were 3 (1.4), and almost half of these patients had, at some point, been registered to have 1 or more non-modifiable risk factors in addition to their age. In conclusion, risk factors that may impact treatment with oral Janus kinase inhibitors were frequent in Danish adults with atopic dermatitis, especially among older individuals. Dermatologists need support and continuously updated long-term safety data when risk-evaluating patients with atopic dermatitis prior to initiation of advanced.

Demographics, characteristics and medical treatment among adults with hand eczema in Denmark. A cross-sectional validation and registry-based study.

BACKGROUND: The international classification of diseases, 10th revision (ICD-10) includes several unvalidated diagnostic codes for hand eczema (HE). Knowledge is sparse on HE patient characteristics. OBJECTIVES: To validate selected HE ICD-10 codes in the Danish National Patient Registry (DNPR) and describe disease characteristics, lifestyle factors and medication use in adult HE patients. METHODS: Nineteen HE ICD-10 codes were selected and validated based on patient charts. Five cohorts were constructed based on the diagnostic code, DL30.8H (HE unspecified), in the DNPR: (i) patients with DL30.8H code (n = 8386), (ii) patients with DL30.8H code, but without atopic dermatitis (AD) (n = 7406), (iii) sex- and age-matched general population (n = 8386) without HE. Two additional cohorts nested in the DNPR included participants from the Danish Skin Cohort, (iv) patients with DL30.8H code but without AD (n = 1340) and (v) general population cohort (n = 9876). RESULTS: ICD-10 codes revealed positive predictive values ≥90% except irritant contact dermatitis (unspecified) (79.7%) and hyperkeratotic hand and foot eczema (84.1%). HE patients were most often women, middle-aged or older, of Danish ethnicity, had an atopic medical history and were smokers. Topical corticosteroid prescriptions were almost doubled in HE cohorts compared to general populations. CONCLUSION: We validated several HE ICD-10 codes and identified important HE patient characteristics.

Sex differences in adverse events from systemic treatments for psoriasis: A decade of insights from the Swiss Psoriasis Registry (SDNTT).

BACKGROUND: Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies. OBJECTIVES: To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs). METHODS: Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex. RESULTS: In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87-9.68) compared to CSTs (7.08, CI 5.39-9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females. CONCLUSION: Females were associated with a significantly higher rate of ADRs and drug-related discontinuation rates. Sex stratification should be taken into consideration when designing studies in the patient-tailored management of psoriasis.

Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, and phase 2b trial (IASOS).

BACKGROUND: Orismilast is a novel oral phosphodiesterase-4 (PDE4) B/D inhibitor being investigated as a potential treatment for moderate-to-severe psoriasis. OBJECTIVE: To evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis. METHODS: This multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy end points were analyzed using multiple imputation. RESULTS: Of 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast vs placebo. Orismilast showed significant improvements in the primary end point, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast -52.6% to -63.7% and placebo, -17.3%; all P <.001). Greater proportions receiving orismilast achieved PASI75 (39.5%-49.0%; P <.05) and PASI90 (22.0%-28.3%; P <.05 for 20 and 40 mg) vs placebo (PASI75, 16.5% and PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed. LIMITATIONS: Small sample size, disease severity imbalance between groups, limited duration and diversity in study population. CONCLUSION: Orismilast demonstrated greater efficacy vs placebo and a safety profile in line with PDE4 inhibition.

Atopic dermatitis phenotypes based on cluster analysis of the Danish Skin Cohort.

BACKGROUND: Despite previous attempts to classify atopic dermatitis (AD) into subtypes (e.g. extrinsic vs. intrinsic), there is a need to better understand specific phenotypes in adulthood. OBJECTIVES: To identify, using machine learning (ML), adult AD phenotypes. METHODS: We used unsupervised cluster analysis to identify AD phenotypes by analysing different responses to predetermined variables (age of disease onset, severity, itch and skin pain intensity, flare frequency, anatomical location, presence and/or severity of current comorbidities) in adults with AD from the Danish Skin Cohort. RESULTS: The unsupervised cluster analysis resulted in five clusters where AD severity most clearly differed. We classified them as 'mild', 'mild-to-moderate', 'moderate', 'severe' and 'very severe'. The severity of multiple predetermined patient-reported outcomes was positively associated with AD, including an increased number of flare-ups and increased flare-up duration and disease severity. However, an increased severity of rhinitis and mental health burden was also found for the mild-to-moderate phenotype. CONCLUSIONS: ML confirmed the use of disease severity for the categorization of phenotypes, and our cluster analysis provided novel detailed information about how flare patterns and duration are associated with AD disease severity.